Mast cells, known for their involvement in allergic reactions where they secrete numerous chemicals in response to immunoglobulin E and specific antigens, have recently been localized in the central nervous system. The function of these brain mast cells has remained speculative as they have not been the subject of any combined functional or detailed morphological studies. Here it is shown that these cells are primarily perivascular and stain metachromatically with Toluidine Blue, but red with Alcian Blue counterstained with Safranin, indicating that they contain proteoglycans quite similar to those of peritoneal, but not mucosal mast cells. Intracardiac administration of the classic mast cell secretagogue, compound 48/80, or the acetylcholine analog, carbachol, caused ultrastructural changes in brain mast cells consistent with secretion, but without exocytosis. However, it is known that the same concentration of carbachol has no effect on homogeneic peritoneal mast cells. These results indicate that brain mast cells share histochemical characteristics with serosal mast cells, but differ in their reactivity to secretagogues, and apparently in the mechanism of secretion. Their ability to respond to neurotransmitters and their distinct mechanism of secretion, which may be selective, expands their possible role in brain pathophysiology.